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101.
The Similarity Principle provides the conceptual framework behind most modern approaches to library sampling and design. However, it is often the case that compounds which appear to be very similar structurally may in fact exhibit quite different activities toward a given target. Conversely, some targets recognize a wide variety of molecules and thus bind compounds that have markedly different structures. Affinity fingerprints largely overcome the difficulties associated with selecting compounds on the basis of structure alone. By describing each compound in terms of its binding affinity to a set of functionally dissimilar proteins, fundamental factors relevant to binding and biological activity are automatically encoded. We demonstrate how affinity fingerprints may be used in conjunction with simple algorithms to select active-enriched diverse training sets and to efficiently extract the most active compounds from a large library. 相似文献
102.
RA Garrott SL Monfort PJ White KL Mashburn JG Cook 《Canadian Metallurgical Quarterly》1998,34(1):126-131
In utero hypoxia may affect the development of the brain and result in altered respiratory responses postnatally. Using a barometric plethysmograph, we examined the effects of exposing pregnant guinea pigs to 200 ppm carbon monoxide (CO) for 10 h/d from d 23-25 of gestation until term (approximately 68 d) on the ventilatory responses of their 4-5-d-old neonates at rest, and during progressive asphyxia and steady state hypercapnia. Exposure to this concentration of CO produced significantly higher levels of carboxyhemoglobin (COHb) in maternal (8.53 +/- 0.6% versus 0.25 +/- 0.1%) and fetal blood (13.0 +/- 0.4% versus 1.6 +/- 0.1%) from CO-treated animals when compared with controls. Hematocrit was significantly higher in the CO-treated neonates (46.3 +/- 1.0% versus 41.3 +/- 0.9%) at 5-6 d of age, although no difference existed between the groups for COHb at this time. There was no difference between the groups for length of gestation, litter size, or birth weight, but CO-treated neonates were significantly smaller at 4 d of age (102.4 +/- 3.7 g) compared with controls (132.0 +/- 5.0 g). At 4-5 d of age there was no difference between the groups for either tidal volume (VT), respiratory frequency (f), or minute ventilation (VE) at rest, but during steady state hypercapnia (4 and 6% CO2) the CO-treated neonates had a significantly greater VT and VE (but not f) than did controls. During progressive asphyxia, CO-treated animals had a significantly greater VT than did controls from 1-8% CO2. There was a significant fall in f at 1 and 3% CO2 in CO-treated animals; however, this effect did not persist, resulting in a significantly increased VE from 3 to 8% CO2. The inspiratory flow rate (VT/expiratory time) was significantly increased in the CO-treated neonates during progressive asphyxia; this occurred in the absence of a difference in inspiratory time between the groups. These results indicate that prenatal exposure to CO increases CO2 sensitivity in 4-5-d-old guinea pigs. This may be due to developmental alterations in the areas of the brainstem responsible for respiratory control. 相似文献
103.
SL Ling 《Canadian Metallurgical Quarterly》1998,39(10):435-436
104.
DM Taylor SL Woodgate AJ Fleetwood RJ Cawthorne 《Canadian Metallurgical Quarterly》1997,141(25):643-649
A pool of scrapie-infected sheep brains was used to spike mixtures of porcine bone and intestine. These were processed in pilot-scale facsimiles of 12 rendering procedures that were in use within the European Union in 1991, and three that were not. Meat and bone meal, and tallow, were produced from the rendered tissues. Suspensions of all the meat and bone meal samples, and two of the tallow samples were assayed in mice for scrapie infectivity. Neither of the tallow samples had any detectable infectivity but the meat and bone meal samples were positive, except for those produced by processes involving exposure to hyperbaric steam. In addition, greaves were produced from the scrapie-spiked raw materials by an atypical low-temperature process and subjected to solvent extraction with hot heptane. The treated greaves were then exposed to steam to drive off residual solvent. Although the starting titre of infectivity in these greaves was low, there appeared to be no reduction in infectivity as a result of the treatments with hot heptane and steam. However, there was no detectable infectivity in the meat and bone meal prepared from the greaves produced by the atypical low-temperature process after it had been exposed to hyperbaric steam. 相似文献
105.
106.
The multilamellate glial sheath of mixed nerve roots of the sixth abdominal ganglion of crayfish contains numerous hemi-desmosomes which appear to attach glial lamellae to material in adjacent extracellular clefts. These junctions, which have been described in detail in an earlier report (Shivers and Brightman, '76), are irregular in shape, punctuate and may be as large as 1 mum in diameter. Surgical interruption of sixth ganglion nerve roots results in regeneration of motor axons and their multilamellate glial sheaths. As the glial processes grow and re-establish a highly organized axon sheath, hemi-desmosomes appear. These junctions are present at the advancing edge of glial processes as well as on their lateral margins. Developing hemi-desmosomes are characterized as a diffuse aggregation of 120-130 A intramembrane particles which are present three weeks following nerve section. As growth and reorganization of the sheath proceeds, the intramembrane particles appear to aggregate and form irregular clusters of varying dimensions. Regenerating nerves freeze-cleaved 8 to 16 weeks following surgery exhibit junctional particle aggregates similar to those in normal unoperated nerve roots. Origin of the intramembrane particles which comprise the junctional aggregated in unknown. Perhaps they are synthesized de novo by the regenerating glial cells or, they may be remnants of complexes which became dispersed following surgery. This is the first report of a freeze-fracture study of hemi-desmosome plasticity in an invertebrate nervous system. 相似文献
107.
108.
109.
110.
The effect of 21 days of promethazine-HC1 administration on hepatic bilirubin metabolism and transport was studied in adult rats. A significant increase in mean cumulative hepatic bilirubin uptake (84.5 +/- 7.6 (SE) mug/100 g/min in controls vs. 110.0 +/- 4.3 in treated rats), mean hepatic glucuronide conjugation (1,330 +/- 86 (SE) mug bilirubin conjugated/g liver/40 min in controls vs. 1.713 +/- 61 in treated rats), and mean maximal hepatic excretion (47.2 +/- 4.9 (SE) mug/100 g/min vs. 63.5 +/- 2.7) was observed in treated animals. Mean total liver weight and total hepatic protein also increased significantly. These observations suggest that promethazine is an inducer of protein and enzyme synthesis in rat liver and is capable of significantly stimulating the three major steps in hepatic disposal of bilirubin. 相似文献